Tag Archives: Cees Dekker

Customizing bacteria (E. coli) into squares, circles, triangles, etc.

The academic paper for this latest research from Delft University of Technology (TU Delft, Netherlands), uses the term ‘bacterial sculptures,’ an intriguing idea that seems to have influenced the artistic illustration accompanying the research announcement.

Artistic rendering live E.coli bacteria that have been shaped into a rectangle, triangle, circle, and square (from front to back). Colors indicate the density of the Min proteins that represent a snapshot in time (based on actual data), as these proteins oscillate back and forth within the bacterium, to determine the mid plane of the cell for cellular division. Image credit:  ‘Image Cees Dekker lab TU Delft / Tremani’

Artistic rendering live E.coli bacteria that have been shaped into a rectangle, triangle, circle, and square (from front to back). Colors indicate the density of the Min proteins that represent a snapshot in time (based on actual data), as these proteins oscillate back and forth within the bacterium, to determine the mid plane of the cell for cellular division.
Image credit: ‘Image Cees Dekker lab TU Delft / Tremani’

A June 22, 2015 news item on Nanowerk provides more insight into the research (Note: A link has been removed),

The E.coli bacterium, a very common resident of people’s intestines, is shaped as a tiny rod about 3 micrometers long. For the first time, scientists from the Kavli Institute of Nanoscience at Delft University have found a way to use nanotechnology to grow living E.coli bacteria into very different shapes: squares, triangles, circles, and even as letters spelling out ‘TU Delft’. They also managed to grow supersized E.coli with a volume thirty times larger than normal. These living oddly-shaped bacteria allow studies of the internal distribution of proteins and DNA in entirely new ways.

In this week’s Nature Nanotechnology (“Symmetry and scale orient Min protein patterns in shaped bacterial sculptures”), the scientists describe how these custom-designed bacteria still manage to perfectly locate ‘the middle of themselves’ for their cell division. They are found to do so using proteins that sense the cell shape, based on a mathematical principle proposed by computer pioneer Alan Turing in 1953.

A June 22, 2015 TU Delft press release, which originated the news item, expands on the theme,

Cell division

“If cells can’t divide properly, biological life wouldn’t be possible. Cells need to distribute their cell volume and genetic materials equally into their daughter cells to proliferate.”, says prof. Cees Dekker, “It is fascinating that even a unicellular organism knows how to divide very precisely. The distribution of certain proteins in the cell is key to regulating this, but how exactly do those proteins get that done?”

Turing

As the work of the Delft scientist exemplifies, the key here is a process discovered by the famous Alan Turing in 1953. Although Turing is mostly known for his role in deciphering the Enigma coding machine and the Turing Test, the impact of his ‘reaction-diffusion theory’ on biology might be even more spectacular. He predicted how patterns in space and time emerge as the result of only two molecular interactions – explaining for instance how a zebra gets its stripes, or how an embryo hand develops five fingers.

MinD and MinE

Such a Turing process also acts with proteins within a single cell, to regulate cell division. An E.coli cell uses two types of proteins, known as MinD and MinE, that bind and unbind again and again at the inner surface of the bacterium, thus oscillating back and forth from pole to pole within the bacterium every minute. “This results in a low average concentration of the protein in the middle and high concentrations at the ends, which drives the division machinery to the cell center”, says PhD-student Fabai Wu, who ran the experiments. “As our experiments show, the Turing patterns allow the bacterium to determine its symmetry axes and its center. This applies to many bacterial cell shapes that we custom-designed, such as squares, triangles and rectangles of many sizes. For fun, we even made ‘TUDelft’ and ‘TURING’ letters. Using computer simulations, we uncovered that the shape-sensing abilities are caused by simple Turing-type interactions between the proteins.”

Actual data for live E.coli bacteria that have been shaped into the letters TUDELFT.
The red color shows the cytosol contents of the cell, while the green color shows the density of the Min proteins, representing a snapshot in time, as these proteins oscillate back and forth within the bacterium to determine the mid plane of the cell for cellular division. The letters are about 5 micron high.
Image credit:  ‘Fabai Wu, Cees Dekker lab at TU Delft’

Spatial control for building synthetic cells

“Discovering this process is not only vital for our understanding of bacterial cell division – which is important in developing new strategies for antibiotics. But the approach will likely also be fruitful to figuring out how cells distribute other vital systems within a cell, such as chromosomes”, says Cees Dekker. “The ultimate goal in our research is to be able to completely build a living cell from artificial components, as that is the only way to really understand how life works. Understanding cell division – both the process that actually pinches off the cell into two daughters and the part that spatially regulates that machinery – is a major part of that.”

Here’s a link to and a citation for the paper,

Symmetry and scale orient Min protein patterns in shaped bacterial sculptures by Fabai Wu, Bas G. C. van Schie, Juan E. Keymer, & Cees Dekker. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.126 Published online 22 June 2015

This paper is behind a paywall but there does seem to be another link (in the excerpt below) which gives you a free preview via ReadCube Access (according to the TU Delft press release),

The DOI for this paper will be 10.1038/nnano.2015.126. Once the paper is published electronically, the DOI can be used to retrieve the abstract and full text by adding it to the following url: http://dx.doi.org/

Enjoy!

A 2nd European roadmap for graphene

About 2.5 years ago there was an article titled, “A roadmap for graphene” (behind a paywall) which Nature magazine published online in Oct. 2012. I see at least two of the 2012 authors, Konstantin (Kostya) Novoselov and Vladimir Fal’ko,, are party to this second, more comprehensive roadmap featured in a Feb. 24, 2015 news item on Nanowerk,

In October 2013, academia and industry came together to form the Graphene Flagship. Now with 142 partners in 23 countries, and a growing number of associate members, the Graphene Flagship was established following a call from the European Commission to address big science and technology challenges of the day through long-term, multidisciplinary R&D efforts.

A Feb.  24, 2015 University of Cambridge news release, which originated the news item, describes the roadmap in more detail,

In an open-access paper published in the Royal Society of Chemistry journal Nanoscale, more than 60 academics and industrialists lay out a science and technology roadmap for graphene, related two-dimensional crystals, other 2D materials, and hybrid systems based on a combination of different 2D crystals and other nanomaterials. The roadmap covers the next ten years and beyond, and its objective is to guide the research community and industry toward the development of products based on graphene and related materials.

The roadmap highlights three broad areas of activity. The first task is to identify new layered materials, assess their potential, and develop reliable, reproducible and safe means of producing them on an industrial scale. Identification of new device concepts enabled by 2D materials is also called for, along with the development of component technologies. The ultimate goal is to integrate components and structures based on 2D materials into systems capable of providing new functionalities and application areas.

Eleven science and technology themes are identified in the roadmap. These are: fundamental science, health and environment, production, electronic devices, spintronics, photonics and optoelectronics, sensors, flexible electronics, energy conversion and storage, composite materials, and biomedical devices. The roadmap addresses each of these areas in turn, with timelines.

Research areas outlined in the roadmap correspond broadly with current flagship work packages, with the addition of a work package devoted to the growing area of biomedical applications, to be included in the next phase of the flagship. A recent independent assessment has confirmed that the Graphene Flagship is firmly on course, with hundreds of research papers, numerous patents and marketable products to its name.

Roadmap timelines predict that, before the end of the ten-year period of the flagship, products will be close to market in the areas of flexible electronics, composites, and energy, as well as advanced prototypes of silicon-integrated photonic devices, sensors, high-speed electronics, and biomedical devices.

“This publication concludes a four-year effort to collect and coordinate state-of-the-art science and technology of graphene and related materials,” says Andrea Ferrari, director of the Cambridge Graphene Centre, and chairman of the Executive Board of the Graphene Flagship. “We hope that this open-access roadmap will serve as the starting point for academia and industry in their efforts to take layered materials and composites from laboratory to market.” Ferrari led the roadmap effort with Italian Institute of Technology physicist Francesco Bonaccorso, who is a Royal Society Newton Fellow of the University of Cambridge, and a Fellow of Hughes Hall.

“We are very proud of the joint effort of the many authors who have produced this roadmap,” says Jari Kinaret, director of the Graphene Flagship. “The roadmap forms a solid foundation for the graphene community in Europe to plan its activities for the coming years. It is not a static document, but will evolve to reflect progress in the field, and new applications identified and pursued by industry.”

I have skimmed through the report briefly (wish I had more time) and have a couple of comments. First, there’s an excellent glossary of terms for anyone who might stumble over chemical abbreviations and/or more technical terminology. Second, they present a very interesting analysis of the intellectual property (patents) landscape (Note: Links have been removed. Incidental numbers are footnote references),

In the graphene area, there has been a particularly rapid increase in patent activity from around 2007.45 Much of this is driven by patent applications made by major corporations and universities in South Korea and USA.53 Additionally, a high level of graphene patent activity in China is also observed.54 These features have led some commentators to conclude that graphene innovations arising in Europe are being mainly exploited elsewhere.55 Nonetheless, an analysis of the Intellectual Property (IP) provides evidence that Europe already has a significant foothold in the graphene patent landscape and significant opportunities to secure future value. As the underlying graphene technology space develops, and the GRM [graphene and related materials] patent landscape matures, re-distribution of the patent landscape seems inevitable and Europe is well positioned to benefit from patent-based commercialisation of GRM research.

Overall, the graphene patent landscape is growing rapidly and already resembles that of sub-segments of the semiconductor and biotechnology industries,56 which experience high levels of patent activity. The patent strategies of the businesses active in such sub-sectors frequently include ‘portfolio maximization’56 and ‘portfolio optimization’56 strategies, and the sub-sectors experience the development of what commentators term ‘patent thickets’56, or multiple overlapping granted patent rights.56 A range of policies, regulatory and business strategies have been developed to limit such patent practices.57 In such circumstances, accurate patent landscaping may provide critical information to policy-makers, investors and individual industry participants, underpinning the development of sound policies, business strategies and research commercialisation plans.

It sounds like a patent thicket is developing (Note: Links have been removed. Incidental numbers are footnote references),,

Fig. 13 provides evidence of a relative increase in graphene patent filings in South Korea from 2007 to 2009 compared to 2004–2006. This could indicate increased commercial interest in graphene technology from around 2007. The period 2010 to 2012 shows a marked relative increase in graphene patent filings in China. It should be noted that a general increase in Chinese patent filings across many ST domains in this period is observed.76 Notwithstanding this general increase in Chinese patent activity, there does appear to be increased commercial interest in graphene in China. It is notable that the European Patent Office contribution as a percentage of all graphene patent filings globally falls from a 8% in the period 2007 to 2009 to 4% in the period 2010 to 2012.

The importance of the US, China and South Korea is emphasised by the top assignees, shown in Fig. 14. The corporation with most graphene patent applications is the Korean multinational Samsung, with over three times as many filings as its nearest rival. It has also patented an unrivalled range of graphene-technology applications, including synthesis procedures,77 transparent display devices,78 composite materials,79 transistors,80 batteries and solar cells.81 Samsung’s patent applications indicate a sustained and heavy investment in graphene R&D, as well as collaboration (co-assignment of patents) with a wide range of academic institutions.82,83

 

image file: c4nr01600a-f14.tif
Fig. 14 Top 10 graphene patent assignees by number and cumulative over all time as of end-July 2014. Number of patents are indicated in the red histograms referred to the left Y axis, while the cumulative percentage is the blue line, referred to the right Y axis.

It is also interesting to note that patent filings by universities and research institutions make up a significant proportion ([similar]50%) of total patent filings: the other half comprises contributions from small and medium-sized enterprises (SMEs) and multinationals.

Europe’s position is shown in Fig. 10, 12 and 14. While Europe makes a good showing in the geographical distribution of publications, it lags behind in patent applications, with only 7% of patent filings as compared to 30% in the US, 25% in China, and 13% in South Korea (Fig. 13) and only 9% of filings by academic institutions assigned in Europe (Fig. 15).

 

image file: c4nr01600a-f15.tif
Fig. 15 Geographical breakdown of academic patent holders as of July 2014.

While Europe is trailing other regions in terms of number of patent filings, it nevertheless has a significant foothold in the patent landscape. Currently, the top European patent holder is Finland’s Nokia, primarily around incorporation of graphene into electrical devices, including resonators and electrodes.72,84,85

This may sound like Europe is trailing behind but that’s not the case according to the roadmap (Note: Links have been removed. Incidental numbers are footnote references),

European Universities also show promise in the graphene patent landscape. We also find evidence of corporate-academic collaborations in Europe, including e.g. co-assignments filed with European research institutions and Germany’s AMO GmbH,86 and chemical giant BASF.87,88 Finally, Europe sees significant patent filings from a number of international corporate and university players including Samsung,77 Vorbeck Materials,89 Princeton University,90–92 and Rice University,93–95 perhaps reflecting the quality of the European ST base around graphene, and its importance as a market for graphene technologies.

There are a number of features in the graphene patent landscape which may lead to a risk of patent thickets96 or ‘multiple overlapping granted patents’ existing around aspects of graphene technology systems. [emphasis mine] There is a relatively high volume of patent activity around graphene, which is an early stage technology space, with applications in patent intensive industry sectors. Often patents claim carbon nano structures other than graphene in graphene patent landscapes, illustrating difficulties around defining ‘graphene’ and mapping the graphene patent landscape. Additionally, the graphene patent nomenclature is not entirely settled. Different patent examiners might grant patents over the same components which the different experts and industry players call by different names.

For anyone new to this blog, I am not a big fan of current patent regimes as they seem to be stifling rather encouraging innovation. Sadly, patents and copyright were originally developed to encourage creativity and innovation by allowing the creators to profit from their ideas. Over time a system designed to encourage innovation has devolved into one that does the opposite. (My Oct. 31, 2011 post titled Patents as weapons and obstacles, details my take on this matter.) I’m not arguing against patents and copyright but suggesting that the system be fixed or replaced with something that delivers on the original intention.

Getting back to the matter at hand, here’s a link to and a citation for the 200 pp. 2015 European Graphene roadmap,

Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems by Andrea C. Ferrari, Francesco Bonaccorso, Vladimir Fal’ko, Konstantin S. Novoselov, Stephan Roche, Peter Bøggild, Stefano Borini, Frank H. L. Koppens, Vincenzo Palermo, Nicola Pugno, José A. Garrido, Roman Sordan, Alberto Bianco, Laura Ballerini, Maurizio Prato, Elefterios Lidorikis, Jani Kivioja, Claudio Marinelli, Tapani Ryhänen, Alberto Morpurgo, Jonathan N. Coleman, Valeria Nicolosi, Luigi Colombo, Albert Fert, Mar Garcia-Hernandez, Adrian Bachtold, Grégory F. Schneider, Francisco Guinea, Cees Dekker, Matteo Barbone, Zhipei Sun, Costas Galiotis,  Alexander N. Grigorenko, Gerasimos Konstantatos, Andras Kis, Mikhail Katsnelson, Lieven Vandersypen, Annick Loiseau, Vittorio Morandi, Daniel Neumaier, Emanuele Treossi, Vittorio Pellegrini, Marco Polini, Alessandro Tredicucci, Gareth M. Williams, Byung Hee Hong, Jong-Hyun Ahn, Jong Min Kim, Herbert Zirath, Bart J. van Wees, Herre van der Zant, Luigi Occhipinti, Andrea Di Matteo, Ian A. Kinloch, Thomas Seyller, Etienne Quesnel, Xinliang Feng,  Ken Teo, Nalin Rupesinghe, Pertti Hakonen, Simon R. T. Neil, Quentin Tannock, Tomas Löfwander and Jari Kinaret. Nanoscale, 2015, Advance Article DOI: 10.1039/C4NR01600A First published online 22 Sep 2014

Here’s a diagram illustrating the roadmap process,

Fig. 122 The STRs [science and technology roadmaps] follow a hierarchical structure where the strategic level in a) is connected to the more detailed roadmap shown in b). These general roadmaps are the condensed form of the topical roadmaps presented in the previous sections, and give technological targets for key applications to become commercially competitive and the forecasts for when the targets are predicted to be met.  Courtesy: Researchers and  the Royal Society's journal, Nanoscale

Fig. 122 The STRs [science and technology roadmaps] follow a hierarchical structure where the strategic level in a) is connected to the more detailed roadmap shown in b). These general roadmaps are the condensed form of the topical roadmaps presented in the previous sections, and give technological targets for key applications to become commercially competitive and the forecasts for when the targets are predicted to be met.
Courtesy: Researchers and the Royal Society’s journal, Nanoscale

The image here is not the best quality; the one embedded in the relevant Nanowerk news item is better.

As for the earlier roadmap, here’s my Oct. 11, 2012 post on the topic.